Reduced glucosylceramide in the mouse model of Fabry disease: Correction by successful enzyme replacement therapy

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Quinta, R (Author) Other; Rodrigues, D (Author) Other; Assuncao, M (Author) Other; Macedo, MF (Author) Other; Azevedo, O (Author) Other; Cunha, D (Author) Other; oliveira, p (Author) ICBAS; Sa Miranda, MCS (Author) Other

Journal

Title: Gene

Vol. 536

Pages: 97-104

ISSN: 0378-1119

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-008-YZS

DOI: 10.1016/j.gene.2013.11.073

Abstract (EN): Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of alpha-Galactosidase A (alpha-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if alpha-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism., glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the liver's GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by alpha-Gal A deficiency.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8